Designing scaffolds to mimic the extracellular matrix and provide a 3D microenvironment that can be remodeled by cells during migration has been an area of growing interest with applications in wound healing, tissue engineering and stem cell expansion. Although such materials provide an initially well-defined microenvironment for the cells, little is known about how migrating cells degrade and remodel synthetic scaffolds. The lack of quantitative and predictable information about this process has limited advances in biomaterial design. To bridge this gap, characterizing a 3D hydrogel matrix remodeled by encapsulated cells using both macro- and microrheological measurements will enable quantitative evaluation of the material properties in the region directly around the cell, the pericellular region, before the onset of and during cell migration. Specifically, we propose experiments to determine material properties and the length scale of scaffold heterogeneity during the degradation reaction. Bulk rheology will be used to supplement microrheology enabling measurements of the complete gelation reaction. Finally, measurements conducted in the presence of an encapsulated migratory cell line, specifically human mesenchymal stem cells, will be performed to better understand how rheological changes in the pericellular region correlate with cell morphology, focal adhesions and motility. This approach to understanding cell migration, focusing on the fundamental rheological changes within the hydrogel, has the potential to transform many fields including but not limited to rheology of soft materials, 3D cell culture, tissue regeneration and biomaterials development.
Broader impacts: The information gained during these studies will increase knowledge about cell remodeling during migration. The proposed research will have a significant impact on the intellectual advances and broader technological developments in several fields including wound healing, tissue engineering and stem cell culture. This will benefit society by advancing the development of biomaterials that can control cellular function, motility and morphology. The results of this work will be disseminated in academic papers and conference presentations. This multidisciplinary project will train students, graduate and undergraduate, with special efforts to recruit students from underrepresented groups. These students will perform research to meet the goals of this project, and this research will also be shared with the community. The PI and her research group have a history of extensive outreach to high school students and teachers and the general public, and the team will work to highlight the impact of biomaterial science in society.
